The anophthalmic mutant mouse provides an animal model for analysing the effect of total prenatal deafferentation on developing and adult visual system. The validity of this model is being defined through light and electron microscopy coupled with the use of tracers to label axoplasmic flow. Previous work in my laboratory had indicated considerable similarity between the dorsal lateral geniculate nucleus (LGd) of anophthalmic and postnatally enucleated mice, except for quantitative differences in the number of neurons and neuroglia. Experimental analysis of the anophthalmic and enucleated mice is being continued to define the connectivity between the LGd and striate cortex (area 17) as well as between the thalamic lateralis posterior (LP) and the striate cortex, through iontophoretic administration of horseradish peroxidase. Our ultrastructural analysis of the anophthalmic LGd demonstrated that retinal afferents are substituted by distinctive large terminals, which are only partly cortical in origin. To determine whether the "substitute terminals" originate from cortical areas which normally do not project to the LGd, hRP has been injected into the LGd and cortical lesions of area 17, 18 and 18a and whole unilateral neocortex decortication are being performed. Because our current work has demonstrated an aberrant pathway between the thalamic LP nucleus and striate cortex in the anophthalmic mutant, we are attempting to determine whether this connection exists after early postnatal enucleation by microiontophoretically injection of HRP into the center of area 17. The development of the visual system of the anophthalmic mutant (day 12, 14, 16, 18 gestation to birth) will be compared to that of the normal control mouse. This comparison may identify in the anophthalmic condition, temporal or abnormal disturbances in the differentiation in the visual centers, and whether or not independent abnormalities exist elsewhere in the central nervous system. Recently, we have demonstrated the presence of well differentiated extraocular muscles in the orbits of anophthalmic mice, as well as the presence of a well-developed oculomotor nucleus.